Potassium Phosphate, Tribasic → (+/-)-8-[5-(1-Ethoxycarbonyl-ethyl)-2-methoxy-phenyl]-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1773988ノート

反応式

HRID 1773988 の反応式
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH2:30]([O:32][C:33](=[O:45])[CH:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[C:38](Br)[CH:37]=1)[CH3:35])[CH3:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:54]([O:61][C:62]([N:64]1[CH2:73][CH2:72][C:71]2[C:66](=[C:67](B3OC(C)(C)C(C)(C)O3)[CH:68]=[CH:69][C:70]=2[F:74])[CH2:65]1)=[O:63])[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1>C1(C)C=CC=CC=1.O.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:54]([O:61][C:62]([N:64]1[CH2:73][CH2:72][C:71]2[C:66](=[C:67]([C:38]3[CH:37]=[C:36]([CH:34]([C:33]([O:32][CH2:30][CH3:31])=[O:45])[CH3:35])[CH:41]=[CH:40][C:39]=3[O:42][CH3:43])[CH:68]=[CH:69][C:70]=2[F:74])[CH2:65]1)=[O:63])[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574588042-(3-Bromo-4-methoxy-phenyl)-propionic acid ethyl esterHCID 896488855-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

生成物 1

HCID 89648690(+/-)-8-[5-(1-Ethoxycarbonyl-ethyl)-2-methoxy-phenyl]-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
100 °C

実験手順

A mixture under N2 of palladium(II)acetate (1.2 mg, 5 μmol, 0.02 eq.), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (4.2 mg, 0.01 mmol, 0.04 eq.), (±)-2-(3-bromo-4-methoxy-phenyl)-propionic acid ethyl ester (80 mg, 0.26 mmol, 1 eq.) and potassium phosphate (109 mg, 0.51 mmol, 2 eq.) in toluene (1.9 mL) and water (0.2 mL) was stirred at r.t. during 2 min. 5-Fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (147 mg, 0.26 mmol, 1 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t., diluted with Et2O (10 mL), filtered through celite, washed with Et2O, and the filtrate was concentrated in vacuo. The residue was purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the title compound as a colorless oil.

後処理

  1. temperatureto cool to r.t.
  2. filtrationfiltered through celite
  3. washwashed with Et2O
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by prep
  6. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

出典と根拠

ORDレコード
ord-d1c76907915f49adae84574116cc81b9
出典データセット
uspto-grants-2016_02
特許番号
US09255090B2

反応ノート

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